Targeting hyaluronan interactions in spinal cord astrocytomas and diffuse pontine gliomas.
Although significant advances have been made in treating malignant pediatric central nervous system tumors such as medulloblastoma, no effective therapy exists for diffuse pontine glioma or intramedullary spinal astrocytoma. Biology of these 2 tumors is poorly understood, in part because diffuse pontine gliomas are not treated surgically, and tumor specimens from intramedullary spinal astrocytomas are rare and minuscule. At the 2007 Neurobiology of Disease in Children Symposium, we presented evidence that malignant glioma behaviors, including antiapoptosis, invasiveness, and treatment resistance, are enhanced by hyaluronan, an extracellular glycosaminoglycan. We review the clinical course of pediatric intramedullary spinal astrocytoma and diffuse pontine glioma, and show expression of membrane proteins that interact with hyaluronan: CD44, extracellular matrix metalloproteinase inducer, and breast cancer resistance protein (BCRP/ABCG2). Furthermore, we describe novel animal models of these tumors for preclinical studies. These findings suggest that hyaluronan antagonism has potential therapeutic value in malignant central nervous system tumors.
Maria
Bernard L
BL
Department of Pediatrics, Charles P Darby Children's Research Institute, College of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. mariabl@musc.edu
Gupta
Nalin
N
Gilg
Anne G
AG
Abdel-Wahab
May
M
Leonard
Anthony P
AP
Slomiany
Mark
M
Wheeler
William G
WG
Tolliver
Lauren B
LB
Babcock
Michael A
MA
Lucas
John T
JT
Toole
Bryan P
BP
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051926:Basigin / Q000235:genetics / Q000378:metabolism; D020295:Brain Stem Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013120:Spinal Cord Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C497886:BSG protein, human; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D051926:Basigin; D006820:Hyaluronic Acid